SULF1 - Function

Function

Heparan sulfate proteoglycans (HSPGs) are widely expressed throughout most tissues of nearly all multicellular species. The function of HSPGs extends beyond providing an extracellular matrix (ECM) structure and scaffold for cells. They are integral regulators of essential cell signaling pathways affecting cell growth, proliferation, differentiation, and migration. Although the core protein is important, the large heparan sulfate (HS) chains extending from the core are responsible for most receptor signaling. HS chains are heterogeneous structures that differ in specific and conditional cell contexts. Of particular importance is the HS sulfation pattern, which was once thought to be static after HS biosynthesis in the Golgi. However, this paradigm changed after the discovery of two extracellular 6-O-S glucosamine arylsulfatases, Sulf1 and Sulf2. These two enzymes allow rapid extracellular modification of sulfate content in HSPGs, impacting signaling involving Shh, Wnt, BMP, FGF, VEGF, HB-EGF, GDNF, and HGF. In addition, Sulfs may exercise another level of regulation over HS composition by down or upregulating HS biosynthetic enzymes present in the Golgi through the very same signaling pathways they modify.

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